Date of Award
Joan C. Edwards School of Medicine
Type of Degree
Dr. Shekher Mohan, Committee Chairperson
Dr. Richard Egleton
Dr. Ashley Seifert
Dr. Omar F. Khan
Dr. Hasan Koc
As the opioid epidemic continues to grow, opioid use among pregnant women is increasing significantly. This has led to a steady rise in the number of infants born with neonatal opioid withdrawal syndrome (NOWS). Although short-term withdrawal symptoms associated with NOWS are well characterized, there are many gaps in our understanding of the short and long-term effects of prenatal opioid exposure. In CHAPTER 1, we describe the clinical presentation, associated neurodevelopmental challenges, and current treatments of NOWS. Our current understanding of the neuropathology of NOWS is limited, and therefore further research is needed. However, current animal models are limited by several confounding factors. In CHAPTER 2, we describe an overview of animal models that have been used to model prenatal opioid exposure and current findings. In CHAPTER 3, we describe a unique rodent species, Acomys cahirinus, which may serve as a more translational model for prenatal opioid exposure. In CHAPTER 4, we describe the use of Acomys cahirinus, more commonly known as spiny mice, to assess the short-term effects of prenatal morphine exposure. We found that prenatal morphine exposure led to an increase in withdrawal behaviors including wall climbing, face cleaning, jumping, wet dog shakes, tremors, and a decrease in ultrasonic vocalizations in spiny mice pups during the early postnatal period (PND 0 -7). Additionally, physiological changes such as increased body temperature and decreased body weight were observed in morphine exposed offspring. Sex differences were observed in the withdrawal behaviors and physiological changes associated with prenatal morphine exposure. In CHAPTER 5, we describe the long-term effects of prenatal morphine exposure on spatial memory in adolescent and adult spiny mice offspring. A deficit in spatial working and reference memory were observed in morphine exposed offspring. These deficits persisted from adolescence to adulthood in a sex specific manner. Additionally, we found that morphine exposed offspring had lower body weights compared to saline that persisted from 1.5 – 3.0 months of age, and was more pronounced in female offspring. In CHAPTER 6, we describe a retrospective chart review of infants born at Cabell Huntington Hospital diagnosed with neonatal abstinence syndrome (NAS) from April 2015 – December 2015. Maternal demographics and drug screening information were collected. Infant information was collected during the first 7 days of life including withdrawal symptoms, treatment, and growth parameters. We found significant gender differences in withdrawal behaviors, time to methadone treatment initiation, and total methadone exposure between male and female infants with NAS. The studies included in this thesis validated the use of a unique rodent species, Acomys cahirinus, to model prenatal opioid exposure. We described the short-term consequences and withdrawal behavior as well as the long-term consequences on memory in this model. Collectively, these studies demonstrated significant gender differences in withdrawal behaviors, postnatal growth, and memory impairments. Future studies will be focused on understanding the underlying molecular changes in the developing spiny mouse brain following prenatal opioid exposure. We hope to find the molecular basis for our observed gender differences. Additionally, we are hopeful that future studies can ascertain potential therapeutic interventions to prevent NOWS in infants prenatally exposed to opioids.
Opioid abuse -- Treatment -- Research.
Drug abuse in pregnancy -- Research.
Infants (Newborn) -- Effect of drugs on -- Research.
Stevens, Sarah, "From crib to bench: understanding Neonatal Opioid Withdrawal Syndrome (NOWS) using a novel rodent model" (2021). Theses, Dissertations and Capstones. 1380.